DNA polymerase θ is preferentially expressed in lymphoid tissues and upregulated in human cancers
DNA polymerase θ is preferentially expressed in lymphoid tissues and upregulated in human cancers
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DOI：
10.1002/ijc.11666
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发表时间：
2004-03-10
影响因子：
6.4
通讯作者：
O-Wang, JY
中科院分区：
文献类型：
--
作者：
Kawamura, K;Bahar, R;O-Wang, JY
DNA聚合酶theta(Pol Theta)是最近发现的一种含有固有解旋酶结构域的A家族聚合酶。果蝇Pol theta突变体对双功能DNA交联剂高度敏感，并表现出较高的自发染色体畸变率，这表明Poll theta在修复DNA链间交联物和维持基因组稳定性方面发挥了作用。为了研究Pol theta在肿瘤发生中的可能作用，我们检测了它在各种正常和恶性组织中的表达。采用逆转录聚合酶链式反应(RT-PCR)、Northern或Western印迹方法检测27例肺癌、28例胃癌、26例结肠癌患者癌旁组织及26例正常人肿瘤组织中Pol theta的表达。Poll theta主要在初级淋巴器官中表达，包括胎肝、胸腺和骨髓，在这些器官中，淋巴祖细胞经历其抗原受体基因的V(D)J重排。此外，Pol theta在生发中心B细胞中表达上调，在B细胞中发生免疫球蛋白基因的类开关重组。Pol theta在匹配的癌组织中的表达检测显示，Pol theta在非肿瘤组织中几乎检测不到，但在27例肺癌中17例(63%)、28例胃癌中11例(39%)和26例结肠癌中20例(77%)表达上调。此外，与表达低水平Pol theta的患者相比，高水平Pol theta表达的患者的临床结果明显较差。这些结果暗示Pol theta可能在淋巴细胞中具有特殊的功能，其过度表达可能有助于肿瘤的进展。(C)2003年Wiley-Liss，Inc.
DNA polymerase theta (Pol theta) is a recently identified family A polymerase that contains an intrinsic helicase domain. Drosophila Pol theta mutants are hypersensitive to bifunctional DNA crosslinking agents and exhibit an elevated frequency of spontaneous chromosomal aberrations, suggesting a role for Poll theta in repair of DNA interstrand crosslinks and in the general maintenance of genome stability. To investigate a possible involvement of Pol theta in tumorigenesis, we have examined its expression in various normal and malignant tissues. Paired tumor and adjacent nontumorous tissues from patients with lung (n = 27), stomach (n = 28) and colon (n = 26) cancer, as well as 26 normal human tissues, were examined for Pol theta expression by RT-PCR, Northern or Western blot analysis. Poll theta was predominantly expressed in primary lymphoid organs including the fetal liver, thymus and bone marrow where lymphocyte progenitors undergo V(D)J rearrangements of their antigen receptor genes. In addition, Pol theta expression was upregulated in germinal center B cells, in which class switch recombination of the immunoglobulin genes occurs. Examination of Pol theta expression in matched cancer specimens revealed that Pol theta was barely detectable in the nontumorous tissues but was upregulated in 17 of 27 (63%) lung, 11 of 28 (39%) stomach and 20 of 26 (77%) colon cancers. Moreover, patients with high levels of Pol theta expression had a significantly poorer clinical outcome compared with those expressing low levels of Pol theta. These results implicate that Pol theta may have a specialized function in lymphocytes and that its overexpression may contribute to tumor progression. (C) 2003 Wiley-Liss, Inc.